Resumption of smoking within 3 months is the most common sequela to a cessation attempt. The relapse process, which begins with a single smoking episode (i.e., a slip or lapse), almost invariably leads to full relapse at some subsequent time point, usually sooner than later. Psychopharmacologically, this sequence of events may be explained by the stimulus priming effect, in which drug-seeking behaviors are reinstated following re-exposure to the drug during a period of abstinence. We propose a series of five interrelated studies to be conducted with both experimental and clinical populations that will systematically examine the effects of experimentally-scheduled smoking lapses and their modulation by nicotine replacement (via patch). For all studies, the experimental model will be to simulate a smoking lapse under controlled laboratory conditions. In this way, we will be able to manipulate and measure the lapse dose (dose effects) as well as document the effects of varying lapse doses on the subsequent relapse behaviors. Two specific models of smoking relapse will be explored; one involves a laboratory choice procedure in which subjects choose between smoking versus abstinence following lapse exposures. In other studies, several prospective natural environment measures of return to smoking over post-exposure days will be measured. Overall, these prospective studies should provide valuable information concerning the biobehavioral processes underlying smoking relapse with specific empirical support for the priming effect and its relationship to smoking relapse. Findings should provide new information about the time course of subjective and physiological effects important in the lapse-to- relapse process. Finally, we aim to provide clinically valuable information concerning the potential relapse prevention utility of nicotine replacement treatment via modulation of stimulus exposure effects.